Kaempferol acts through mitogen‐activated protein kinases and protein kinase B/AKT to elicit protection in a model of neuroinflammation in BV2 microglial cells

Abstract

BACKGROUND AND PURPOSEKaempferol, a dietary flavonoid and phyto-oestrogen, is known to have anti-inflammatory properties. Microglial activation has been implicated in various neurodegenerative diseases. Anti-inflammatory effects of kaempferol and the underlying mechanisms were investigated by using LPS-stimulated microglial BV2 cells. EXPERIMENTAL APPROACHCell viability was measured using MTT and neutral red assays. ELISA, Western blot, immunocytochemistry and electrophoretic mobility-shift assay were used to analyse NO, PGE2, TNF-a and IL-1b production, inducible NOS (iNOS), COX-2 expression and the involvement of signalling pathways such as toll-like receptor-4 (TLR4), MAPK cascades, PKB (AKT) and NF-kB. Accumulation of reaction oxygen species (ROS) was measured by nitroblue tetrazolium and 2′7′-dichlorofluorescein diacetate assay. Matrix metalloproteinase activity was investigated by zymography and immunoblot assay. Phagocytotic activity was assessed by use of latex beads. KEY RESULTSKaempferol significantly attenuated LPS-induced NO, PGE2, TNF-a, IL-1b and ROS production and phagocytosis in a concentration-dependent manner. Kaempferol suppressed the expression of iNOS, COX-2, MMP-3 and blocked the TLR4 activation. Moreover, kaempferol inhibited LPS-induced NF-kB activation and p38 MAPK, JNK and AKT phosphorylation. CONCLUSION AND IMPLICATIONSKaempferol was able to reduce LPS-induced inflammatory mediators through the down-regulation of TLR4, NF-kB, p38 MAPK, JNK and AKT suggesting that kaempferol has therapeutic potential for the treatment of neuroinflammatory diseases. AbbreviationsAKT, PKB; iNOS, inducible NOS; ROS, reactive oxygen species; TLR-4, toll-like receptor-4 (TLR4) BJP British Journal of Pharmacology

Kaempferol induces autophagy through AMPK and AKT signaling molecules and causes G2/M arrest via downregulation of CDK1/cyclin B in SK-HEP-1 human hepatic cancer cells

“…Many protein kinases are involved in the cell survival response, and previous studies suggested that AMPK and AKT serine/threonine kinase [also called protein kinase B (PKB)] play key roles and are involved in the induction of cell autophagy (34,35). AKT activation was associated with anti-apoptotic responses, cell proliferation and cellular energy metabolism.…”

Downregulation of tumor necrosis factor and other proinflammatory biomarkers by polyphenols

“…LPS-mediated TLR2 127 mRNA induction has been shown to be attenuated by curcumin. 128 Curcumin has also been shown to modulate TNF-a function by 129 direct binding to the ligand [23,24]. Wu et al, performed Q2 molecular 130 docking studies and found that curcumin is a potent inhibitor of 131 TNF-a because of its ability to form covalent and non-covalent 132 interactions [25].…”

Optimization, formulation, and characterization of multiflavonoids-loaded flavanosome by bulk or sequential technique

“…It restricts the tumor necrosis factor alpha-mediated NF-κB activation, p38, c-Jun N-terminal kinases (JNK), and protein kinase B (AKT) phosphorylation via suppression of advanced glycation end products-induced nicotinamide adenine dinucleotide phosphate oxidase in both in vitro and in vivo studies. 12,13 Furthermore, K also acts as a potential anticancer agent by modulation of mitogen-activated protein kinases/extracellular signal-regulated kinases (ERK) and phosphoinositide 3-kinase/AKT pathways that represent major signaling routes implicated in cancer development. K plays a highly discriminative role over normal and malignant cells, whereby it induces apoptosis in cancer cells only, while leaving healthy cells unaffected.…”